ABSTRACT  BACKGROUND፡ The majority of population rely on traditional medicine as a source of healthcare. Artemisia afra is a plant traditionally used for its medicinal values, including treatment of malaria in many parts of the world. Currently, it is also attracting attention because of a claim that a related species, Artemisia annua, is a remedy for the COVD-19 pandemic. The aim of the present study was to investigate toxic effects of A. afra on brain, heart and suprarenal glands in mice aged 8-12 weeks and weighing 25-30g.METHODS: Leaves of A.afra were collected from Bale National Park, dried under shade, crushed into powder and soaked in distilled water to yield aqueous extract for oral administration. For acute toxicity study, seven treated and one control groups, with 3 female mice each, were used. They were given a single dose of 200mg/kg, 700mg/kg, 1200mg/kg, 2200mg/kg, 3200mg/kg, 4200mg/kg or 5000mg/kg b/wt of the extract. For the sub-acute toxicity study, two treated and one control groups, with 5 female and 5 male mice each, were used.  They were daily treated with 600mg/kg or 1800mg/kg b/wt of extract.RESULTS: LD50 was found to be greater than 5000mg/kg indicating that the plant is relatively safe. In the sub-acute study, no signs of toxicity were observed in all treatment groups. On microscopic examination of the brain, heart and suprarenal glands no sign of cellular injury was observed. CONCLUSION: The findings of this study suggest that the leaves extract of A. afra is relatively safe in mice.KEYWORDS: A. afra, Toxicity study, histopathology, brain, heart, suprarenal glands, Swiss albino mice